Urinary complications resulting from benign prostatic hyperplasia (BPH) continue to be a major health problem for the elderly male population. In spite of its clinical importance remarkable little is known about the pathogenesis of this condition. The hyperplasia mainly involves the central regions of the gland and is present in both a diffuse and nodular pattern. We believe that elucidation of the mechanism of formation of the hyperplastic nodule will provide general insights into the mechanism(s) of the excessive cell growth that occurs in aging prostates. We have postulated the stromal cell in the prostate is phenotypically distinct from those in the surrounding non-nodular tissue. Consistent with this notion, we have observed that the proteoglycan, versican, is more abundant in the nodular tissues. In very preliminary studies we have observed higher steady state levels of versican mRNA in nodular tissues and in cultures of stromal cells derived from the nodules as compared to those derived from te non- nodular tissue. In this application we are proposing to extend this observation by measuring versican mRNA and protein levels in a series of stromal cell cultures derived from nodular and non-nodular tissues. In separate studies we will measure these mRNA levels in stromal and epithelial cells from nodular and non-nodular tissues isolated by fluorescence-activated flow sorting and/or by laser-assisted capture microscopy. Finally, in studies designed to further define nodule stromal cell phenotype, we will initiate the first stages of a study comparing the gene expression profile of flow-sorted and/or laser- captured stromal and epithelial cells from nodular and non-nodular tissues by hybridization of total cDNA from amplified RNA preparations to microarrays comprised of prostate=derived cDNA.